Context.-Original surgical pathology materials from external sources are reviewed by our pathologists for referred patients before their clinical evaluation and treatment. Objective.-To identify the rate of major disagreements with diagnoses from external institutions and to characterize the nature and impact of discordant diagnoses on patient care. Design.-We identified and reviewed all surgical pathology cases, except for medical liver, medical renal, and cardiac pathology cases, for the period between January 1, 2005, and December 31, 2010, to determine the overall frequency of major disagreements, defined as any change in diagnosis having a substantial impact on patient management. Results.-Our review of 71 811 cases initially examined between 2005 and 2010 identified 457 major disagreements (0.6%). The most frequent areas of disagreement were gastrointestinal (80 cases; 17.5%), lymph node (73; 16.0%), bone/soft tissue (47; 10.3%), and genitourinary (43; 9.4%). For a subset of 166 cases reviewed between July 1, 2009, and December 31, 2010, follow-up data were available for 140 (84.3%). Treatment was affected by a changed diagnosis in 126 cases (90.0%), and prognosis was affected in 129 cases (92.1%). For 86 (51.8%) of the 166 cases, additional tissue was obtained. Revised diagnoses concurred with follow-up tissue diagnosis in 84.9% (73 cases), whereas they differed from follow-up tissue diagnosis in 15.1% (13 cases). Conclusions.-Our findings demonstrate the value of outside case review of pathology materials for referred patients, and suggest that it decreases the likelihood of diagnostic errors and provides better protection for patients.